Progress in DNA sequencing has occurred through multiple stages of disruptive new technologies being introduced to the field, each of which has increased sequencing capabilities by lowering costs, improving throughput, and reducing errors. The goal of this research project is to investigate a new, all-electronic sequencing method that has the potential to become the next transformative step for DNA sequencing. This new method is based on single DNA polymerase molecules bound to nanoscale electronic transistors, a hybrid device that transduces the activity of a single polymerase molecule into an electronic signal. The goal of this research project is to determine whether these hybrid polymerase-transistors are truly applicable to DNA sequencing and the competitive environment of advanced sequencing technologies. To answer this question, the project teams the scientists who have developed the devices with Illumina, Inc., a worldwide leader in the DNA sequencing market. The experiments proposed here build on encouraging preliminary results, first to demonstrate accurate DNA sequencing and second to evaluate whether the new technique could become a competitive challenge to other sequencing methods. The interdisciplinary team will combine state-of-the-art techniques from protein engineering, nanoscale fabrication, and machine learning to customize polymerase's activity and its interactions with the electronic transistors. If successful, nanoscale solid-state devices like transistors provide one of the best opportunities for increasing sequencing capabilities while decreasing sequencing costs, so that DNA sequencing can become a standard technique in health care and disease treatment.